Combined Effects of Dibutyl Phthalate (DBP) and Benzo(a)Pyrene on Fertility in Male Rats

Our previous studies revealed the polycyclic aromatic hydrocarbon and phthalic acid esters were the major organic pollutants in the Jialing River and Yangtze River in the Three Gorges area, and they might cause the toxicity in male fertility when combined. Thus we used di-n-butyl phthalate (DBP) and Benzo(a)pyrene (Bap) as their representatives respectively to explore their effects on the spermatogenesis in male rats. Male Sprague Dawley rats were randomly divided into 4 groups and respectively exposed to corn oil, Bap (5 mg/kg/d), DBP (250 mg/kg/d), and combined doses of Bap (5 mg/kg/d) and DBP (250 mg/kg/d) for 90 days. We observed a significant increase in the stillbirth rate after Bap and combined treatments, while the mean area of seminiferous tubules was reduced after Bap, DBP and combined treatments. Bap and combined treatment had a sup- pressing effect on meiosis in germ cells, which reduced the haploid contents and the ratio between haploid and diploid but increased the tetraploid and diploid contents and the ratio between hap- loid and tetraploid. These effects were more obvious in the combined group. Furthermore, the ex- pression of a number of proteins was changed, of which was associated with the oxidative stress and cAMP/PKA signaling pathway. Our results suggest that Bap has significant toxic effects on male fertility, while the combined treatment of Bap and DBP has more toxic effects.

Nanotechnology’s frontier in combatting infectious and inflammatory diseases:prevention and treatment

Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases,which continuously pose one of the most serious threats to human health,attributed to factors such as the emergence of new pathogens,increasing drug resistance,changes in living environments and lifestyles,and the aging population.Despite rapid advancements in mechanistic research and drug development for these diseases,current treatments often have limited efficacy and notable side effects,necessitating the development of more effective and targeted anti-inflammatory therapies.In recent years,the rapid development of nanotechnology has provided crucial technological support for the prevention,treatment,and detection of inflammation-associated diseases.Various types of nanoparticles(NPs)play significant roles,serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability.NPs can also directly combat pathogens and inflammation.In addition,nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases.This review categorizes and characterizes different types of NPs,summarizes their applications in the prevention,treatment,and detection of infectious and inflammatory diseases.It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects.In conclusion,nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.

Human cytomegalovirus miR-US5-1 inhibits viral replication by targeting Geminin mRNA

Viruses commonly create favorable cellular conditions for their survival through multiple mechanisms. Micro RNAs(mi RNAs), which function as post-transcriptional regulators, are utilized by human cytomegalovirus(HCMV) in its infection and pathogenesis. In the present study, the DNA replication inhibitor Geminin(GMNN) was identified to be a direct target of hcmv-mi R-US5-1. Overexpression of hcmv-mi R-US5-1 could block the accumulation of GMNN during HCMV infection, and the decrease of GMNN expression caused by hcmv-mi R-US5-1 or GMNN specific si RNA reduced HCMV DNA copies in U373 cells. Meanwhile, ectopic expression of hcmv-mi R-US5-1 and consequent lower expression of GMNN influenced host cell cycle and proliferation. These results imply that hcmv-mi R-US5-1 may affect viral replication and host cellular environment by regulating expression kinetics of GMNN during HCMV infection.

Human Cytomegalovirus Influences Host circRNA Transcriptions during Productive Infection

Human cytomegalovirus(HCMV)is a double-strand DNA virus widely infected in human.Circular RNAs(circ RNAs)are non-coding RNAs with most functions of which keep unknown,and the effects of HCMV productive infection on host circ RNA transcriptions remain unclear.In this study,we profiled 283 host circ RNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts(HELF)by RNA deep sequencing and bioinformatics analysis.Among these,circ SP100,circ MAP3 K1,circ PLEKHM1,and circ TRIO were validated for their transcriptions and sequences.Furthermore,characteristics of circ SP100 were investigated by RT-q PCR and northern blot.It was implied that circ SP100 was produced from the sense strand of the SP100 gene containing six exons.Kinetics of circ SP100 and SP100 m RNA were significantly different after infection:circ SP100 levels increased gradually along with infection,whereas SP100 m RNA levels increased in the beginning and dropped at 24 h post-infection(hpi).Meanwhile,a total number of 257 proteins,including 10 HCMV encoding proteins,were identified potentially binding to cytoplasmic circ SP100 by RNA antisense purification(RAP)and mass spectrometry.Enrichment analysis showed these proteins were mainly involved in the spliceosome,protein processing,ribosome,and phagosome pathways,suggesting multiple functions of circ SP100 during HCMV infection.

Gut microbiome,cognitive function and brain structure:a multi-omics integration analysis

Background:Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes,but evidence from large human cohorts is lacking.This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations.Methods:We included 1430 participants from the Guangzhou Nutrition and Health Study(GNHS)with both gut microbiome and cognitive assessment data available as a discovery cohort,of whom 272 individuals provided fecal samples twice before cognitive assessment.We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit.Fecal 16S rRNA and shotgun metagenomic sequencing,tar-geted serum metabolomics,and cytokine measurements were performed in the GNHS.The validation analyses were conducted in an Alzheimer’s disease case-control study(replication study 1,n=90)and another community-based cohort(replication study 2,n=1300)with cross-sectional dataset.Results:We found protective associations of specific gut microbial genera(Odoribacter,Butyricimonas,and Bac-teroides)with cognitive impairment in both the discovery cohort and the replication study 1.Result of Bacteroides was further validated in the replication study 2.Odoribacter was positively associated with hippocampal volume(β,0.16;95%CI 0.06-0.26,P=0.002),which might be mediated by acetic acids.Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment.We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition.Conclusions:Our findings reveal that specific gut microbial features are closely associated with cognitive impair-ment and decreased hippocampal volume,which may play an important role in dementia development.

Human cytomegalovirus RNA2.7 inhibits RNA polymeraseⅡ(PolⅡ)Serine-2 phosphorylation by reducing the interaction between PolⅡand phosphorylated cyclin-dependent kinase 9(pCDK9)

Human cytomegalovirus(HCMV)is a ubiquitous pathogen belongs to betaherpesvirus subfamily.RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20%of total viral transcripts.In our study,functions of HCMV RNA2.7 were investigated by comparison of host cellular transcriptomes between cells infected with HCMV clinical strain and RNA2.7 deleted mutant.It was demonstrated that RNA polymeraseⅡ(PolⅡ)-dependent host gene transcriptions were significantly activated when RNA2.7 was removed during infection.A145 nt-in-length motif within RNA2.7 was identified to inhibit the phosphorylation of PolⅡSerine-2(PolⅡS2)by reducing the interaction between PolⅡand phosphorylated cyclin-dependent kinase 9(pCDK9).Due to the loss of PolⅡS2 phosphorylation,cellular DNA pre-replication complex(pre-RC)factors,including Cdt1 and Cdc6,were significantly decreased,which prevented more cells from entering into S phase and facilitated viral DNA replication.Our results provide new insights of HCMV RNA2.7 functions in regulation of host cellular transcription.

Correction to:Human Cytomegalovirus Influences Host circRNA Transcriptions during Productive Infection

The information of affiliation 1 and 3 was incorrect.The information of affiliations should read as given below.Author information 1 Virology Lab,Shengjing Hospital of China Medical University,Shenyang 110004,China 2 Department of Laboratory,Central Hospital Affiliated to Shenyang Medical College,Shenyang 110024,China.